St Louis J D, Lederer J A, Lichtman A H
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Exp Med. 1993 Nov 1;178(5):1597-605. doi: 10.1084/jem.178.5.1597.
The ability of endothelial cells to activate helper T (Th) cells by antigen presentation was studied using the murine endothelial cell line SVEC4-10 and antigen-specific murine T cell clones. SEVEC4-10 cells constitutively express vascular cell adhesion molecule 1 but not intercellular adhesion molecule 1. Interferon gamma (IFN-gamma) treatment of these cells induced class II major histocompatibility complex (MHC) expression and antigen-presenting capabilities, but did not alter surface integrin expression. IFN-gamma-treated SVEC4-10 cells were competent at mediating antigen-dependent cytokine production and proliferation of a Th2 clone. In contrast, endothelial antigen presentation to Th1 cells did not stimulate T cell proliferation. The addition of MHC mismatched spleen cells as a source of costimulatory molecules resulted in the ability of the endothelial cells to stimulate Th1 cell proliferation in an antigen-specific manner. The failure of the endothelial cell line alone to support Th1 cell proliferation correlated with the failure to stimulate interleukin 2 (IL-2) gene expression. T cell exposure to the endothelial cells plus antigen resulted in upregulation of IL-2 receptors and an enhanced response to subsequent antigen presentation by splenic antigen-presenting cells. Despite the lack of functional costimulators for IL-2 expression, antigen presentation by the endothelial cell line did not induce Th1 cell anergy, indicating that costimulator deficiency for IL-2 expression is not obligatorily linked to anergy induction. Thus, endothelial cells are capable of presenting antigens to helper T lymphocytes, but stimulate only partial T cell responses. These partial responses may serve to selectively stimulate transmigration of antigen-specific T cells and may enhance functional responses upon subsequent, extravascular antigen exposure.
利用小鼠内皮细胞系SVEC4-10和抗原特异性小鼠T细胞克隆，研究了内皮细胞通过抗原呈递激活辅助性T（Th）细胞的能力。SEVEC4-10细胞组成性表达血管细胞黏附分子1，但不表达细胞间黏附分子1。用干扰素γ（IFN-γ）处理这些细胞可诱导II类主要组织相容性复合体（MHC）表达和抗原呈递能力，但不会改变表面整合素的表达。经IFN-γ处理的SVEC4-10细胞能够介导抗原依赖性细胞因子的产生以及Th2克隆的增殖。相比之下，内皮细胞向Th1细胞呈递抗原并不能刺激T细胞增殖。添加MHC不匹配的脾细胞作为共刺激分子的来源，可使内皮细胞以抗原特异性方式刺激Th1细胞增殖。单独的内皮细胞系无法支持Th1细胞增殖，这与无法刺激白细胞介素2（IL-2）基因表达有关。T细胞暴露于内皮细胞加抗原会导致IL-2受体上调，并增强对随后脾抗原呈递细胞抗原呈递的反应。尽管缺乏用于IL-2表达的功能性共刺激分子，但内皮细胞系的抗原呈递并未诱导Th1细胞无反应性，这表明IL-2表达的共刺激分子缺陷并非必然与无反应性诱导相关。因此，内皮细胞能够向辅助性T淋巴细胞呈递抗原，但仅刺激部分T细胞反应。这些部分反应可能有助于选择性刺激抗原特异性T细胞的迁移，并可能增强随后血管外抗原暴露时的功能反应。
